Adenosine triphosphate-binding cassette (ABC) transporters form a ubiquitous superfamily of integral membrane proteins involved in the translocation of substrates across membranes. Human ABC transporters are closely linked to the pathogenesis of diseases such as cancer, metabolic diseases, and Alzheimer's disease. In this study, four ABC transporters were chosen based on (I) their importance in humans and (II) their score in a structural bioinformatics screen aimed at the prediction of crystallisation propensity. The top-scoring ABC transporters' orthologs (-mouse ABCB5, -giant panda ABCB6, -little brown bat ABCG1 and ABCG4) were then expressed in with a combined green fluorescent protein and polyhistidine tag, enabling visualisation and purification. After partial purification and in the presence of the detergent (n-dodecyl-β-D-maltoside), the kinetic parameters of the ATP hydrolysis reactions of the orthologs were determined, as well as the extent of stimulation of their activity when presented with putative substrates. We discuss the efficiency of such bioinformatics approaches and make suggestions for their improvement and wider application in membrane protein-structure determination.
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http://dx.doi.org/10.3390/membranes15010020 | DOI Listing |
Pharmaceuticals (Basel)
January 2025
Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Jalan Lagoon Selatan, Bandar Sunway 47500, Selangor, Malaysia.
: The multiple drug-resistant phenomenon has long since plagued the effectiveness of various chemotherapies used in the treatment of patients with glioblastoma (GBM), which is still incurable to this day. ATP-binding cassette (ABC) transporters function as drug transporters and have been touted to be the main culprits in developing resistance to xenobiotic drugs in GBM. : This review systematically analyzed the efficacy of ABC transporters against various anticancer drugs from 16 studies identified from five databases (PubMed, Medline, Embase, Scopus, and ScienceDirect).
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Endocrinology Research Center, Moscow 117292, Russia.
Analyzing the genetic architecture of hereditary forms of diabetes in different populations is a critical step toward optimizing diagnostic and preventive algorithms. This requires consideration of regional and population-specific characteristics, including the spectrum and frequency of pathogenic variants in targeted genes. As part of this study, we used a custom-designed NGS panel to screen for mutations in 28 genes associated with the pathogenesis of hereditary diabetes mellitus in 506 unrelated patients from Russia.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
State Key Laboratory of Crop Genetics and Germplasm Enhancement, Nanjing Agricultural University, Nanjing 210095, China.
Using male sterile (MS) lines instead of normal inbred maternal lines in hybrid seed production can increase the yield and quality with lower production costs. Therefore, developing a new MS germplasm is essential for maize hybrid seed production in the future. Here, we reported a male sterility gene , cloned from a newly found MS mutant .
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Department of Medical, Surgical and Neurological Sciences, University of Siena, 53100 Siena, Italy.
Obesity is a global epidemic associated with chronic inflammation, oxidative stress, and metabolic disorders. Bariatric surgery is a highly effective intervention for sustained weight loss and the improvement of obesity-related comorbidities. However, post-surgery nutritional deficiencies, including vitamin E, remain a concern.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Mechanistic Toxicology Branch, Division of Translational Toxicology, National Institutes of Environmental Health Sciences (NIH), Research Triangle Park, Durham, NC 27709, USA.
Acquired resistance to chemotherapeutic drugs is the primary cause of treatment failure in the clinic. While multiple factors contribute to this resistance, increased expression of ABC transporters-such as P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and multidrug resistance proteins-play significant roles in the development of resistance to various chemotherapeutics. We found that Erastin, a ferroptosis inducer, was significantly cytotoxic to NCI/ADR-RES, a P-gp-expressing human ovarian cancer cell line.
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